The development and introduction of surgical materials is a growing field of research, and the biocompatibility of device materials can influence the outcome of a surgery. Medical devices that come into contact with blood are prone to cause damage, leading to conditions such as thrombosis and platelet aggregation. For example, balloon inflation during angioplasty can damage the endothelial lining in cells, which causes blood vessels to narrow, restricting blood flow. Recurrence of this condition leads to restenosis. Anticoagulants can be prescribed in conjunction with the use of blood contacting devices to reduce the chance of blood damage. However, continual use leads to side effects, including greater chance of hemorrhaging. Not only can devices cause issues for the patient, but the device's clinical performance can be affected. If a device were thromboresistant, these issues would be relieved. Due to its discovery as an inhibitor of platelet aggregation, nitric oxide (NO) has become a widely studied molecule for polymeric materials in biomedical applications.
Nitric Oxide (NO) is a molecule that is produced naturally in the body through enzymatic processes. NO aids in several functions in the body, including wound healing. It is produced during the inflammatory and proliferative phases of wound healing, and is used by the body to transition from the first to the second phase. One of the functions of NO in wound healing is that it acts as a vasodilator, widening blood vessels and helping blood to flow in body tissue. Not only does NO aid in healing, but it also serves as an antibacterial agent. This could be beneficial to all phases of the wound healing process. When incorporating NO into medical devices, the number of complications from wounds resulting from surgical procedures, diabetic lesions, burns and cancer, could potentially decrease.
For the effects of NO delivery to be positive, an appropriate concentration of the drug must be administered. A coating on the polymer will enable a controlled release of NO into the biological system. This coating improves stability; preventing NO from spontaneously releasing from the polymer. It can also allow higher storage retention.
Furthermore, nitric oxide plays an important role in several physiological functions, including immune responses, blood clotting, vasodilation, pulmonary hypertension, and neurotransmission. By incorporating NO into surgical materials, prevention from infections and enhanced wound healing would be possible. Synthesized in the body by nitric oxide synthase (NOS), oxygen reacts with the amino acid L-arginine to produce NO and L-citrulline. NO has been shown to be an antimicrobial agent. NO is produced initially at a higher concentration, to clear out bacterial infection, and then held at lower concentrations, to allow for the wound healing process to begin. It has been shown in the literature that application of NO to wounds can promote the healing process. This process occurs due to the fact that NO is also the endothelium derived relaxing factor. Upon NOS activation, NO signals smooth muscle to relax, causing vasodilation of blood vessels to occur. While NO also inhibits platelet aggregation and inflammatory cell activation, it can be applied as a thrombo-resistant molecule capable of enhanced wound healing purposes when incorporated into polymer surgical materials.
Due to its capability to prevent inflammation and increase blood flow, storage and delivery of nitric oxide has recently become extensively studied for biological purposes. Several classes of NO donor molecules exist, these include organic nitrates, organic nitrites, metal-NO complexes, nitrosamines, nitrosamines, nitrosothiols, and furoxans. A special class of NO adducts are the diazeniumdiolates, or NONOates. Diazeniumdiolates are desirable due to their general stability, and ability to spontaneously release NO at physiological temperature and pH. Diazeniumdiolates, which contain the [N(O)NO]-functional group, release two molar equivalents of NO, with half-lives ranging from 2 seconds to 20 hours. The 2 moles of NO are generally released by a proton source such as humidity or acids, and can also be released by heat or photolysis.
Polyacrylonitrile (PAN) is an important material for producing carbon fibers, and used in many applications, largely in the sporting goods and aerospace industries. Native PAN does not bind NO. After undergoing stabilization, however, the α-hydrogen on the cyano group becomes more acidic and allows NO to bind. In the stabilization process, PAN is treated thermally to allow for the cyano groups to undergo intra-molecular nitrile reaction. Formation of the diazeniumdiolate group on PAN has also been achieved using a strong base for stabilization. Some of the disadvantages associated with thermally treated and strong base-treated include the inability to further manipulate the compositions derived from these methods to form medical devices or other useful objects that can release NO. Therefore, it would be desirable to develop compositions comprising PAN that can bind NO without the requirement for heat treatment or treatment with strong bases.